U.S. scientists have entered into the first clinical trial of extracting stem cells that create sperm and implanting them back into the body to induce sperm production. It appears that a path to restore reproductive ability for men who cannot produce sperm, such as those who have undergone cancer treatment or have certain genetic disorders, may soon open.
Researchers from the University of Pittsburgh Medical Center's Magi Reproductive Transplant Center, the University of Texas MD Anderson Cancer Center, the Oregon National Primate Research Center, and the George Washington University Children's National Hospital have successfully implanted cryopreserved spermatogonial stem cells (SSC) from a U.S. man in his early 20s. This clinical trial was also published on the preprint site for medical research, medRxiv, on the 26th of last month.
Spermatogonial stem cells are cells capable of producing sperm through a differentiation process, found in the seminiferous tubules of male testes. These stem cells create sperm through a very complex process of gene expression and hormonal regulation. If there are irregularities in gene and hormone regulation or if the stem cells are damaged due to chemotherapy for cancer treatment, it can lead to azoospermia and infertility.
Azoospermia, characterized by the absence of sperm in semen, affects 1% of men worldwide. Experts estimate that in the U.S., approximately 645,000 men aged 20-50 suffer from azoospermia. In South Korea, the number of patients receiving infertility treatment increased by 16.9% over the past five years since 2017. During the same period, the number of men receiving infertility treatment increased more than twelvefold. The causes of infertility include azoospermia (absence of sperm in ejaculate), asthenozoospermia, oligozoospermia, and varicocele. Azoospermia is considered a 100% cause of infertility.
Currently, methods for extracting sperm from the testicles are somewhat effective but result in scarring during the procedure and involve significant expenses. Scientists are focusing on spermatogonial stem cells that produce sperm.
The research team used a non-invasive ultrasound-guided seminiferous tubule retrieval (UGRT) approach to locate sperm in the testes or to inject the patient's spermatogonial stem cells into the testes of men with azoospermia. They inserted a needle into the rete testis, a network of small tubules within the testes that produce sperm, using ultrasound guidance to collect the stem cells. The collected stem cells are cryopreserved and can later be thawed and placed in the sperm tubules of the testes to regenerate sperm. Scientists successfully implanted spermatogonial stem cells in male rats and monkeys to enable them to give birth.
This research team has applied this technology to humans for the first time. They implanted stem cells into a man in his 20s who underwent treatment for osteosarcoma from 2011 to 2025 and had cryopreserved his testicular tissue to preserve his fertility during puberty before he developed azoospermia after chemotherapy. The researchers reimplanted the cryopreserved stem cells into the man’s testes, maintaining a normal state without side effects. Levels of key hormones, such as testosterone, follicle-stimulating hormone, and luteinizing hormone, were also recorded normally. The research team plans to analyze semen every two years to check for the presence of reproductive cells.
No traces of sperm generation have yet been found in the patient's semen after the stem cell implantation. The researchers noted that by only collecting a small amount of stem cells to minimize risks during adolescence, the quantity of sperm produced is likely low. As a result, there may be a limited number of cells that produce sperm, leading to low sperm production.
There are methods even if the quantity of sperm produced by stem cells is low. If a patient wants to have children, even if there is not much sperm in the semen, sperm produced in small quantities by the stem cells can be retrieved through surgical methods.
Dr. Laura Gemmill, a reproductive and endocrinology fellow at Columbia University's Reproductive Center, developed a technology separate from this study called the sperm tracing recovery (STAR) system. This machine, which combines artificial intelligence (AI), robotics, and microfluidics, identifies and retrieves the scarce sperm cells found in male semen. It takes just one sperm and one egg to achieve pregnancy. In fact, the researchers previously succeeded in harvesting and cryopreserving ovarian stem cells from girls who had cancer in childhood, and subsequently through implantation, they enabled them to become pregnant.
Like other medical procedures, this technology carries some risks. The implanted cells could have genetic mutations, which could potentially lead to tumors. The risk is even higher if the stem cells come from a patient who had leukemia.
While the patient's own stem cells are used, there are concerns that the immune system might react and cause inflammation. Additionally, obtaining consent during the stem cell collection process from underage patients remains a challenge.
Including this study, research on infertility using spermatogonial stem cells has recently gained attention both domestically and internationally. A research team led by Professor Lee Dong-ryul at CHA University’s Cha Hospital's Women’s Health Research Institute announced in 2019 that they had developed technology to multiply and culture human spermatogonial stem cells contained in the testes for over six months. The research team believes that long-term culture of spermatogonial stem cells outside the body could allow for male infertility treatment using stem cells without genetic manipulation.
Scientists believe that these studies could eventually provide options for young patients who wish to have children. In an interview with Science Live, Justin Horman, a professor at Cedars-Sinai Medical Center, who did not participate in this research, stated, “If the technology improves and safety is proven, it can innovatively restore reproductive abilities to men who have lost the ability to produce sperm,” and added, “It could particularly benefit cancer survivors who received treatment before puberty or men suffering from genetic or acquired sexual dysfunction.”
References
medRxiv (2025), DOI: https://doi.org/10.1101/2025.03.25.25324518